UA155375U - A method for assessing the risk of rapid progression of chronic kidney disease in patients with pre-dialysis chronic kidney disease - Google Patents

Abstract

A method of assessing the risk of rapid progression of chronic kidney disease in patients with pre-dialysis chronic kidney disease includes determining urinary uromodulin levels. Patients with pre-dialysis chronic kidney disease additionally have their urine albumin determined. The ratio of urinary albumin to urinary uromodulin is calculated. The results are compared with the glomerular filtration rate and comorbidity index of these patients. If the value of the urine albumin/uromodulin ratio is more than 5.24 μg/mL, then it is considered a high risk of rapid progression of chronic kidney disease.

Description

A useful model belongs to medicine, particularly nephrology, and can be used to assess the risk of rapid progression of chronic kidney disease (CKD) in patients with pre-dialysis CKD.

CKD is a global medical, social, and economic burden not only in Ukraine, but throughout the world. CKD is diagnosed in 10-16 95 of the adult population of the world (1295 of the population of Ukraine).

Despite the introduction of more modern technologies, the problem of diagnosing rapid progression of CKD is still not solved |11.

CKD is diagnosed if the estimated glomerular filtration rate (GFR) for 3 months or more is less than 60 ml/min/1.73 m and/or the urine albumin/creatinine ratio is more than 30 mg/g. There are five stages (1-5) of CKD, which are determined on the basis of RSKF (Table 1). In the first stage of CKD, kidney function is preserved (there are only confirmed laboratory-instrumental changes in the kidneys), and in stage 5 (end-stage kidney disease), severe renal failure is associated, which requires renal replacement therapy. Stage C includes Za and ZB, which corresponds to "slightly or moderately reduced" and "moderately or severely reduced" kidney function (11.

Table 1

Normal

KOISO (Kiapeu Oizeavze: Itrgomipd Spoba! Oshcisotev) or Moderately Severe 2012: Prognosis of CKD, based on CKF and albuminuria slightly | increased | increased increased "3 mg/mmol 230 mg/mmol mg/mmol risk risk risk risk risk risk . - - Very risk risk risk - - Very Very risk risk risk

Very Very Very

C4 Sharply reduced 15-29 high high high risk risk risk

C5 Very Very Very 00000 | Renal failure -15 high high high 00000 risk risk risk

Note. 7 In the absence of other markers of kidney damage or CKD. GP11 rRSHKF is estimated using the plasma creatinine level conversion formula

Collaborating on the epidemiology of chronic obstructive pulmonary disease

ERI)) (Table 2). rSHCKF, normal, 95:20 ml/min/1.73 m: in women and 125 ml/min/1.73 m? in men (up to years). Annually, after 30 years, GFR decreases by 1 ml/min/1.73 m? (11. A decrease in GFR of more than 5 ml/min/1.73 me/year is considered a rapid progression of CKD.

Table 2

SKO-ERI equation, 2009 (modification from 2011)

Note: Cg is the concentration of creatinine in blood serum; CSH, mg/100 ml - Cg (μmol/l) x 0.0113. (1)

To date, a number of methods for diagnosing and predicting rapid progression have been developed

CKD based on the definition of morphological factors and a complex of metabolic disorders.

However, almost all studies are quite difficult to perform and require the use of expensive equipment and consumables.

An analogue is the method of predicting the rapid decline of kidney function in diabetes (patent Mo 20170115310A1, 5) 2), based on a comprehensive examination of patients with diabetes with the determination of more than 200 biomarkers and the creation of a mathematical model for determining the possibility of the risk of CKD progression. The task was solved by conducting a laboratory examination of patients with diabetes and an assessment with the determination of more than 200 biomarkers, followed by statistical processing of the research results. Making a prognostic decision takes place in several stages. However, this method of diagnosis is multi-component, financially expensive, complicated and inconvenient and only concerns the prediction of the risk of rapid progression of CKD in patients with diabetes.

Also, there is a way to assess the progression of CKD in patients with stage I-I of CKD (patent Mo 124884,

OA) ISI, which differs in that it additionally determines the change in the concentration of uric acid in the blood serum against the background of a water-salt load of 0.595 sodium chloride solution based on 0.5 95 of body weight and in case of its increase or decrease by less than 5 mmol/ l predict a higher risk of CKD progression, which is accompanied by a decrease in GFR.

The disadvantages of this method are: the time-consuming nature of this method, namely, the patient must receive a water-salt load of 0.5 95 sodium chloride solution based on 0.5 95 of his body weight, which, firstly, can negatively affect his health and, secondly, a significant number of CKD 3 patients have contraindications to water-salt loading due to the risk of edema.

Also, this method can be used only in patients with CKD stages I-III, but early diagnosis of rapid progression of CKD is also relevant for patients with CKD stage II.

The closest analogue of a useful model is the method of early diagnosis of rapid progression of CKD in patients with primary glomerulonephritis (patent Mo 146363 OA) |4|, which includes laboratory and clinical studies and determination of CKF and additional research

From the concentration of uric acid in the blood serum during the patient's first visit and on the basis of these data, the progression of CKD in patients to primary glomerulonephritis is diagnosed. However, the disadvantages of this method are: an increase in the concentration of uric acid in blood serum may be associated with other metabolic processes in the body and therefore is not a highly specific marker of rapid progression of CKD. Also, this method can be used for early diagnosis of rapid progression of CKD only in the case of primary glomerulonephritis.

The task of a useful model is to develop an effective method of assessing the risk of rapid progression of CKD in patients with pre-dialysis CKD.

The task is solved by the fact that in the method of assessing the risk of rapid progression of chronic kidney disease in patients with pre-dialysis chronic kidney disease, which includes determining the level of urinary uromodulin, according to a useful model, in patients with pre-dialysis CKD, urinary albumin is additionally determined, the ratio of urinary albumin and uromodulin is calculated urine, compare the obtained results with the glomerular filtration rate and the comorbidity index in these patients, if the value of the urine albumin/uromodulin ratio is more than 5.24 μg/ml, then it is considered a high risk of rapid progression of chronic kidney disease.

The earliest (preclinical) marker of kidney damage is the level of microalbuminuria (from 30 to 300 mg/day or from 20 to 200 mg/ml in spot (morning) portion of urine). Albumin is synthesized in the liver (molecular weight about 65 kDa). The normal blood level in adults is within 35-53 g/l. Normally, a small amount of albumin, with the smallest size (microalbumin), is excreted in the urine, since the glomeruli of an intact kidney are impermeable to larger albumin molecules, which are negatively charged.

Uromodulin, also known as Tamm-Horsfall protein, is the most abundant protein in healthy human urine. Uromodulin is a 90 kDa protein produced exclusively by epithelial cells in the kidneys, which line the thick ascending limb of Henle's loop and distal tubules. In the lumen of tubules, uromodulin forms high-molecular threads that are part of the matrix of hyaline cylinders. Uromodulin is prone to strong glycation, which accounts for 30-40 95 of its total molecular weight, and has a low isoelectric point (ri 5.00). in a polyacrylamide gel with sodium dodecyl sulfate |5|.

The authors came to this decision after conducting research. 122 patients were examined: 91 patients with pre-dialysis CKD, whose average age was 47, 12.12 years. Thirty (32.97 95) men and 61 (67.03 95) women, who were divided into two groups, which were representative in terms of age and tender composition: 1st group (n-46) - patients with CKD 1-5 Art., which had an index

From Charlson's comorbidity x 2, the 2nd group (n-45) - patients with CKD 1-5 stages, who had Charlson's comorbidity index g 3.

The control group included 31 patients aged 22 to 45 years without risk factors for CKD and without signs of kidney damage, with urine uromodulin levels from 2.73 to 3.33 μg/ml (mean value 3.04 μg/ml). The values of the albumin/uromodulin ratio of urine in healthy people were obtained for the first time. Their oscillation range is 1.58-5.24.

The criteria for including patients in the study were: availability of results of laboratory and instrumental examinations, age from 18 to 64 years, patient's consent to participate in the study, ability to adequately cooperate in the research process.

Exclusion criteria from the study were: patient refusal, mental disorders, decompensation of chronic diseases, acute emergency conditions, severe liver diseases, oncology.

The diagnosis of CKD was established according to the recommendations of the National Nephrological Union (MKE-

K/00O0I) of the USA, KOISO criteria of 2012 and in accordance with the order of the Ministry of Health of Ukraine No. 593 dated 02.12.2004 (as amended by the order of the Ministry of Health of Ukraine No. 384 dated 24.05.2012) (11.

The following indicators were determined in the patients at the first stage of the study: urinary uromodulin, urinary albumin, comorbidity index, GFR (Table 3).

The method of determining the level of uromodulin in urine is as follows. Urine samples (average portion) collected in the morning were distributed into test tubes (1.5 ml) immediately after collection. All urine samples were stored at a temperature of -20 C. Urinary uromodulin was measured using a commercially available kit for enzyme immunoassay (EGIZA) (Ogibepe TespppoIodiee Strn,

Herford, Germany). ELISA characteristics provided by the manufacturer: the name is a highly sensitive sandwich EGISA kit for the quantitative determination of uromodulin in human urine (Nitap Ogotoaiip/itoa

EPISODE OF KI); 96 holes, with arrows; sensitivity "10 pg/ml; detection range 312 pg/ml - 20000 pg/ml; at 4 "C storage for b months, at -20"C - for 12 months. The level of urinary uromodulin was measured using a photometer at a wavelength of 450 nm and a reference wavelength of 620 nm. The study was carried out on an immunoenzyme analyzer KT-6100 (Kauo I yiye Apa Apaiuiisa! Zsiepsez5 So., Tsa., People's Republic of China).

The calibrated curve corresponds to the range and norms of the manufacturer of this reagent and the example of the standard curve given by him, which was part of the reagent: Nitap Ogotoatsiip/itoa 60 EPZA Kyiv (EATO2492).

The Shapirko-Wilk test was used to assess the data distribution. Normally distributed data were presented as mean and standard deviation (data presented as

Ma5O), with abnormal - presented as median and lower and upper quartiles (data presented as Me(Og) (01, Oz)).

Pearson's correlation was used to assess association at baseline. Linear regression was performed with the dependent variable and independent variables. Correlation analysis and multiple regression analysis were performed using the Pearson correlation coefficient (g). A p-value of 0.05 was considered statistically significant.

Mathematical analysis and statistical processing of the results was carried out using "Mysgozoic Ehsei! 2010" on a PC.

The study was approved by the Ethics Commission of the National University of Health Care of Ukraine named after P.L. Shupyka

Table C

Indicators of examination of patients at the beginning of the study

Glen beteyaeetia 1 telvtisyuu | trolley

Ratio 4.55597015(4.0 (PalblSt) ' 5.17118644

Note. " The data are presented as M-5O, with a normal distribution, or 02 (C, Oz) - with an abnormal distribution.

At the second stage of the research, statistical processing of the results was done. The results of the study showed that the linear regression between the indicators of pAlb/Sh and rSHKF is statistically significant (p<0.05) in all groups, and between the indicators of imAlb/Sh and the index of comorbidity - only in the second group (Table 4).

Since in the second group, two indicators have p<0.05, the multiple linear regression equation was applied. The results of the multiple linear regression of the indicators of the second group indicate the presence of a weak cumulative significant effect between shAlb/shShpt, the comorbidity index and RSKF, (Р(1.43) - 5.06, р - 0.030, B: - 0.11, B: additional - 0.08) (Fig. 1).

In the control group, the correlation (K) between cAlb/Sh and GFR is -0.5875 - there is a moderate inverse relationship (increase in CAlb/hs by 1 - the value of GFR decreases by 3.6798 (Bog- 3.798 SIC-5.6048, -1 ,75491)) (Fig. 2). CC? - 0.3452 (means that 34.595 of the variability of рРШКФ is explained by cAlb/shШШt).

In the first group, between pAlb/pc and rSHKF, K is -0.3812 - there is a weak inverse relationship (an increase in ChAIB/shSh by 1 - the value of pKhF decreases by 0.7566 (bo--0.7566 CI|- 1.3142, - 0.19911)) (Fig. 3). Kk? - 0.1453 (means that 14.5 95 of the variability of RSKF is explained

From PAlb/ШЩt).

In the second group, between cAlb/Sht and the comorbidity index E is -0.2994 - there is a weak direct relationship (an increase in shAIB/pSht by 1 - the value of the comorbidity index increases by 0.03091 (ro-0.03091 С1(0.0006177 , 0.06121)) (Fig. 4). Kk? - 0.08965 (means that 995 of the variability of the comorbidity index is explained by shAlb/Sht).

In the second group, between chAlb/pSh and rSHKF K is -0.3245 - there is a weak inverse relationship (increasing shAIr/sh by 1 - the value of RHKF decreases by 0.9123 (bo--0.9123 SIC-1.73, - 0 ,094541)) (Fig. 5). K2- 0.1053 (means that 10.5 95 of the variability of RSKF is explained by pAlb/Sht).

Table 4

Linear regression p-Z1 p-46. . 0.3287 0.09949 0.2994 -0.5875 -0.3812 -0.3245

Note: "The data are plotted as K (p).

The method is confirmed by the following examples:

Example 1.

Patient F., 29 years old. Diagnosis: CKD of the II century. (EGFR 69.3 ml/min/1.73 m"), interstitial nephritis.

Urine albumin/uromodulin index at the time of the first visit to the clinic was 6.02. Comorbidity index - 1. After 1 year of observation, the patient's GFR was 61.2 ml/min/1.73 m".

Example 2.

Patient R., 53 years old. Diagnosis: CKD of the II century. (GFR 51.5 ml/min/1.73 m"), gouty nephropathy.

The urine albumin/uromodulin index at the time of the first visit to the clinic was 4.91. The comorbidity index is 3. After 1 year of observation, the patient's GFR was 52.2 ml/min/1.73 m.

Thus, if the value of the urine albumin/uromodulin index is more than 5.24 μg/ml, it is possible to predict a rapid progression of CKD (decrease in GFR »5.0 ml/min/1.73 me/year). The method is a highly informative marker of rapid progression of CKD (sensitivity and specificity of the method is 275 95), which allows timely detection of a high risk of rapid progression

CKD and take appropriate preventive measures and, thus, slow down the rate of progression of CKD. The index of comorbidity, as shown by the results of statistical processing and which were confirmed by the examples given, is an uninformative indicator.

Sources of information: 1. Osepoma 10, Imapom 00. EmaiYinayop oi She ipaeh oi gezibitapse apa ehsteiop oi igotoatsshiip ip rayepov my rgediauvzie spgopis Kidpeu adibzease, iaKipd ipio assocpi She ipdeh oi sotogbiainu.

OKg.U.Kidpeuv. 2023:2(12):26-41. doi: pNr//doi.oga/10.22141/2307-1257.12.2.2023.403 PP OKugaipiapi. 2. Patent No. 20170115310A1 05, IPC C01M 33/6893, B01M 33/50, SObE 19/3431, C0O1M 33/70. Rgedisiipa garia aesiipe ip hepai! tipsiip ip aiarbeiie5z/ Soinotsp N., I ooKeg N., Mekeidne R.,

Soishtro M., Yuipdeg O., Yuakop M., Vgozpap Mu., ModoseKe E., AdaKkom R., Ne55 5., publ. 27.04.2017. 3. Patent No. 124884 OA, IPC S01M 33/50. A method of assessing the progression of chronic kidney disease in patients with stage I-II CKD/ L.M. Savytska, publ. 25.04.2018. 4. Patent Mo 146363 OA, IPK Ab1B 10/00, AbIR 13/12, 501M 33/48. The method of early

On the diagnosis of rapid progression of chronic kidney disease in patients with primary glomerulonephritis/ Stepanova N.M., Snisar L.M., Lebid L.O., Kolesnyk M.O., publ. 02/17/2021. 5. Oepoma 0. Ogotodyiiyp az a roiepiya! sapaidae taiKeg og rgedisiipd She soshtsgze oi SKO.

OKg.U.Kidpeub5. 202154(10):71-77. doi: NOrz//doi.oga/10.22141/2307-1257.10.4.2021.247898 (p

IOKhaipiapi.

Claims (1)

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